Taxols A and B are also known in the literature as taxol and cephalomannine and taxol C has no other name [Mise en evidence nouveaux analogues du taxol extracts de Taxus baccata. V.Senilh, S. Blechert, M. Colin, D. Guenard, F. Picot, P. Potier and P. Verenne, Journal of Natural products 47, 131-137 (1984)].
Out of the three taxols A,B,C, only taxol A (=taxol) is used clinically for the treatments of ovarian and breast cancers. Various types of cancers have been treated with taxol A and the results in the treatments of ovarian and breast cancers are very promising. Taxol A (=taxol) has been approved by the Food and Drug Administration (FDA) of the United States for the treatments of ovarian and breast cancers.
Taxol B (=cephalomannine) has been isolated from the leaves, stems, roots of Taxus wallichiana; It is not clinically used. [Antileukemic alkaloids from Taxus wallichiana. R. W. Miller, R. G. Powell, C. R. Smith, Jr., E. Arnold and J. Clardy, Journal of organic Chemistry 46, 1469-1474 (1981)].
Taxol C has been isolated from the roots of Taxus media [Taxol analogues from the roots of Taxus media. L. Barboni, P. Gariboldi, E. Torregiani, G. Appendino, B. Gabetta and E. Bombardelli, Phytochemistry 36, 987-990 (1994)]. Taxol C has also been isolated from the cell cultures of Taxus baccata and it showed potent and selective cytotoxicity against cell lines of non-small-cell lung cancer, small cell lung cancer, colon cancer, CNS cancer and ovarian cancer; [New bioactive taxoids from cell cultures of Taxus baccata. W. Ma, G. L. Park, G. A. Gomez, M. H. Nieder, T. I. Adams, J. S. Aynsley, O. P. Sahai, R. J. Smith, R. W. Stahlhut, P. J. Hylands, F. Bitsch and C. shackleton, Journal of Natural Products 57, 116-122 (1994)].
Taxol A, a highly oxygenated diterpenoid molecule and a potent anticancer drug was first isolated from the stem bark of Taxus brevifolia. Thereafter, it has also been isolated from other Taxus species including Taxus wallichiana. Taxol A, a structurally complicated and chemically labile molecule needed special and careful extraction and separation procedures for its isolation from plant materials. Unfortunately, most of works are proprietary in nature and have not been published. The American workers have used alcohol to extract taxol from the stem bark of T. brevifolia and isolation of taxol from the alcoholic extract used sequential column chromatography over silica with methanol-chloroform mixture (2:98) as the eluting solvent to yield a mixture of taxol A (=taxol) and Taxol B (cephalomannine). In one of the prior art process. Taxol A has been separated and isolated from the mixture containing taxol A and Taxol B with a yield of 0.01% either by repeated column chromatography over silica gel or by high performance liquid chromatography (HPLC). [M. C. Wani, H. I. Taylor, M. E. Wall, P. Coggan and A. T. Mc Phail. Plant antitumor agents VI: The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia, Journal of the American Chemical Society 93, 2325 (1971); and J. H. Cardellina: HPLC separation of taxol and cephalomannine, Journal of liquid chromatography 14, 659(1991)].
According to another prior art process, Taxol A has been isolated from the stem bark of Taxus wallichiana with a yield of 0.02%. The isolation process involves extracting the stem bark with methanol, partitioning of the methanolic extract between water and chloroform and isolation of taxol A from the chloroform soluble fraction by column chromatography over silica gel [S. K. Chattopadhyay, V. K. Tripathi, R. S. Thakur, R. P. Sharma and S. P. Jain. Isolation of taxol, 10-deacetyl baccatin III and (-) betuligenol from Taxus Baccata Indian J. Chem. 33B,409 (1994)]
10-deacetyl taxol A and C are important precursors as they can be converted into taxol A and C. Moreover, 10-deacetyl taxol A is the starting material for many newly developed analogues of taxol A. 10-DAT, A can be isolated with a yield of 0.0021% from the ethanolic extract of the roots, stems and needles of T. wallichiana by repeated column chromatography over silica gel followed by high pressure liquid chromatography [J. L. Mclaughlin, R. W. Miller, P. G. Powell and C. R. Smith, Jr. 19-hydroxy baccatin III, 10-deacetyl caphalomannine and 10-deacetyl taxol, new antitumor taxanes from Taxus wallichiana. Journal of natural Products 44,312-319 (1981)].
10-deacetyl taxol C has been isolated from the cell cultures of Taxus baccata with a yield of 0.0001%. [New bioactive taxoids from cell cultures of Taxus baccata. W. Ma, G. L. Park, G. A. Gomez, M. H. Nieder, T. I. Adams, J. S. Aynsley, O. P. Sahai, R. J. Smith, R. W. Stahlhut, P. J. Hylands, F. Bitsch and C. Shackleton, Journal of Natural Products 57,116-122 (1994)].
According to a prior art process, the taxol analogues 7-xylosyl-10-deacetyl taxols A,B,C of the formula (1) where R represents C.sub.6 H.sub.5 (taxol analogue A), or CH.sub.3 C.dbd.CHCH.sub.3 (taxolanalogue B) or, C.sub.5 H.sub.11 (taxol analogue C) can be isolated from the stem bark of the Himalayan yew. Taxus wallichiana with higher yields in which no solvent partitioning has been used to isolate the analogues. The yields of 7-xylosyl-10-deacetyl taxols A,B and C obtained were 0.5, 0.02 and 0.0075% respectively. The process comprises extracting air dried pulverized plant materials with alcohols at room temperature, evaporating the solvent to obtain a residue, stirring the resultant residue with water to obtain a thick precipitate, isolating the analogues 7-xylosyl-10deacetyl-taxol A, 7-xylosyl-10-deacetyl taxol B, and 7-xylosyl-10-deacetyl taxol C from the precipitate by flash chromatography over a bed of silica gel [A process for the production of taxol. S. K. Chattopadhyay, R. P. Sharma, Sushil Kumar, K. P. Madhusudanan, Eurorean patent application No. 97306905.7-1521, Dec. 2, 1997].
According to a prior art process, taxol analogues 7-xylosyl-10-deacetyl taxol A and B have been converted into taxol A (=taxol) and taxol B (cephalomannine) by K. V. Rao [Process for the preparation of taxol and 10-deacetyl taxol, K. V. Rao, U.S. patent application Ser. No. 851,469, Mar. 13, 1992]. The process for the preparation of taxol A or B involved reacting the analogue 7-xylosyl-10-deacetyl taxol A or B with periodate in methanol, chloroform and sulphuric acid mixture at 20-60.degree. C. to give a dialdehyde product which was then treated with phenylhydrazine in methanol-aqueous acid mixture and heated at 50-60.degree. C. to degrade the dialdehyde into 10-deacetyl taxol A or B which was then isolated by column chromatography.
The process for preparation of the 10-deacetyl A or B as described by Rao suffers from disadvantages which include (a)--low yield of the 10-deacetyl taxol A or B, (b)--carrying out the periodate oxidation of the 7-xylosyl-10-deacetyl taxol A or B in presence of mineral acid (although it is mentioned by Rao in his patent application that periodate oxidation can also be carried out under neutral condition in presence of excess sodium bicarbonate, the presence of excess dissolved sodium carbonate may lead to degradation of the side chain from dialdehyde leading to a mixture of products, and (c) heating the periodate oxidation product with phenyl hydrazine in methanol-aqueous acetic acid mixture at 50-60.degree. C. to degrade the periodate oxidation product into 10-deacetyl taxol A or B. Moreover, the process for the production of 10-deacetyl taxol C from the analogue 7-xylosyl-10-deacetyl taxol C has not been covered by Rao in his patent application.
According to another prior art process developed by Chattopadhyay et al, the 7-xylosyl-10-deacetyl taxols A, B and C can be converted into 10-deacetyl taxol A, B and C [A process for the production of taxol. S. K. Chattopadhyay, R. P. Sharma, Sushil Kumar and K. P. Madhusudanan, European Patent Application No. 97306905.7-1521, Dec. 2, 1997]. The process for the preparation of 10-deacetyl taxol A or B or C involved dissolving the analogue 7-xylosyl-10-deacetyl taxol A or B or C in a polar solvent, reaching the resultant solution with periodate to cleave the diol system of the xyloside into dialdehyde, reducing the dialdehyde solution in a mixture of polar solvent-acetic acid mixture with borohydride, acidifying the resultant acetal with mineral acid in a chlorinated solvent to yield 10-deacetyl taxol A or B or C.
Although the process developed by Chattopadhyay et al is superior to Rao process in terms of yield of 10-deacetyl taxol A or B or C, it has more steps to get the products.